tbuckley/cabot-search huggingface dataset:
Diffuse midline glioma invasion and metastasis rely on cell-autonomous signaling
Authors: Marco Bruschi, Lilia Midjek, Yassine Ajlil, Stephanie Vairy, Manon Lancien, Samia Ghermaoui, Thomas Kergrohen, Maite Verreault, Ahmed Idbaih, Carlos Alberto Oliveira de Biagi, Ilon Liu, Mariella G Filbin, Kevin Beccaria, Thomas Blauwblomme, Stephanie Puget, Arnault Tauziede-Espariat, Pascale Varlet, Volodia Dangouloff-Ros, Nathalie Boddaert, Gwenael Le Teuff, Jacques Grill, Guillaume Montagnac, Nadia Elkhatib, Marie-Anne Debily, David Castel
Journal: Neuro-Oncology (2023)

Abstract Background Diffuse midline gliomas (DMG) are pediatric tumors with negligible 2-year survival after diagnosis characterized by their ability to infiltrate the central nervous system. In the hope of controlling the local growth and slowing the disease, all patients receive radiotherapy. However, distant progression occurs frequently in DMG patients. Current clues as to what causes tumor infiltration circle mainly around the tumor microenvironment, but there are currently no known determinants to predict the degree of invasiveness. Methods In this study, we use patient-derived glioma stem cells (GSCs) to create patient-specific 3D avatars to model interindividual invasion and elucidate the cellular supporting mechanisms. Results We show that GSC models in 3D mirror the invasive behavior of the parental tumors, thus proving the ability of DMG to infiltrate as an autonomous characteristic of tumor cells. Furthermore, we distinguished 2 modes of migration, mesenchymal and ameboid-like, and associated the ameboid-like modality with GSCs derived from the most invasive tumors. Using transcriptomics of both organoids and primary tumors, we further characterized the invasive ameboid-like tumors as oligodendrocyte progenitor-like, with highly contractile cytoskeleton and reduced adhesion ability driven by crucial over-expression of bone morphogenetic pathway 7 (BMP7). Finally, we deciphered MEK, ERK, and Rho/ROCK kinases activated downstream of the BMP7 stimulation as actionable targets controlling tumor cell motility. Conclusions Our findings identify 2 new therapeutic avenues. First, patient-derived GSCs represent a predictive tool for patient stratification in order to adapt irradiation strategies. Second, autocrine and short-range BMP7-related signaling becomes a druggable target to prevent DMG spread and metastasis.
Error in Abstract and Table
Journal: JAMA Network Open (2023)

Katherine Rizzolo, MD; Rebeca Gonzalez Jauregui, BS; Ileana Barrientos, MD; Jade Teakell, MD, PhD; Claudia Camacho, BS; Michel Chonchol, MD; Sushrut S. Waikar, MD39, MPH; Lilia Cervantes, MD, MSCS
Concordance of the ACR TI-RADS Classification With Bethesda Scoring and Histopathology Risk Stratification of Thyroid Nodules
Authors: Elaine Y. F. Huang, Nern Hoong Kao, Snow Yunni Lin, Isabelle J. H. Jang, Kimberley Liqin Kiong, Anna See, Nanda Venkatanarasimha, Kristen Alexa Lee, Chwee Ming Lim
Journal: JAMA Network Open (2023)

Importance Although most thyroid nodules are benign, 10% to 15% of them harbor cancer. Thyroid ultrasonography is useful for risk stratification of nodules, and American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) classification provides recommendations for fine-needle aspiration cytology (FNAC) based on objective ultrasonographic features of these nodules. Objective To validate the concordance of ACR TI-RADS classification with Bethesda classification and histopathology. Design, Setting, and Participants This retrospective cohort study was performed to evaluate the concordance of ACR TI-RADS classification with Bethesda classification and histopathology and was conducted in Singapore General Hospital Outpatient Otolaryngology clinic in March 2021 to May 2021. Data analysis was performed in May 2021. Main Outcomes and Measures Results were deemed concordant when ACR TI-RADS recommendations aligned with Bethesda scores. Conversely, results were classified as nonconcordant with Bethesda scores and/or histopathology results when nodules that were recommended for FNAC yielded benign results or nodules that were not recommended for FNAC yielded malignant results. Results A total of 446 patients (370 women [83%]; mean [range] age, 60 [24-89] years) who underwent ultrasonography of the thyroid and ultrasonography-guided thyroid FNACs were identified. A total of 492 of 630 nodules (78.1%) were benign on FNAC (Bethesda II). Score 3 ACR TI-RADS nodules yielded the highest negative predictive values: 94.6% (95% CI, 92.9%-95.9%; P &amp;amp;lt; .001) compared with Bethesda scoring and 100.0% (95% CI, 15.8%-100.0%; P = .003) compared with histopathology. Score 4 or 5 ACR TI-RADS nodules yielded positive predictive values of 2.8% and 16.2%, respectively, compared with Bethesda scoring and 6.1% and 66.7%, respectively, compared with histopathology. Small (&amp;amp;lt;1.5 cm) ACR TI-RADS nodules of scores of 4 and 5 that were not recommended for FNAC yielded a malignant risk of 5.7% and 25.0% on Bethesda 5 and 6, respectively. On surgical excision, 5 of 46 (10.9%) ACR TI-RADS 4 nodules and 15 of 21 (71.4%) of ACR TI-RADS 5 nodules were confirmed to be malignant. Among nodules initially not recommended for FNAC, histopathology-proven cancer was found in 4 of 13 (30.7%) and 3 of 6 (50.0%) of nodules, respectively. Conclusions and Relevance These findings suggest that ACR TI-RADS score 3 nodules have a low risk of cancer and should be considered for FNAC only if nodules are 2.5 cm or larger. Patients with small (&amp;amp;lt;1.5 cm) ACR TI-RADS 4 and 5 nodules should be appropriately counseled for FNAC to exclude cancer.
US Deaths From Overdoses Involving Fake Pills Have Increased
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Heart failure patients with improved ejection fraction: Insights from the <scp>MECKI</scp> score database
Authors: Piergiuseppe Agostoni, Francesca Romana Pluchinotta, Elisabetta Salvioni, Massimo Mapelli, Arianna Galotta, Alice Bonomi, Damiano Magrì, Enrico Perna, Stefania Paolillo, Ugo Corrà, Rosa Raimondo, Rocco Lagioia, Roberto Badagliacca, Pasquale Perrone Filardi, Anna Apostolo, Michele Senni, Annamaria Iorio, Michele Correale, Jeness Campodonico, Pietro Palermo, Mariantonietta Cicoira, Marco Metra, Marco Guazzi, Giuseppe Limongelli, Mauro Contini, Beatrice Pezzuto, Gianfranco Sinagra, Gianfranco Parati, Gaia Cattadori, Cosimo Carriere, Marco Cittar, Maria Vittoria Matassini, Andrea Salzano, Antonio Cittadini, Marco Masè, Francesco Bandera, Maurizio Bussotti, Irene Mattavelli, Federica Re, Carlo Vignati, Carlo Lombardi, Angela B. Scardovi, Susanna Sciomer, Andrea Passantino, Michele Emdin, Andrea Di Lenarda, Claudio Passino, Caterina Santolamazza, Federica Moscucci, Denise Zaffalon, Massimo Piepoli
Journal: European Journal of Heart Failure (2023)
Etiologic Studies of Premenstrual Disorders Require Prospective Confirmation of Affective Cyclicity—Reply
Authors: Piotr Jaholkowski, Marit Haram, Ole A. Andreassen
Journal: JAMA Psychiatry (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Effects of 4 Interpretive Front-of-Package Labeling Systems on Hypothetical Beverage and Snack Selections
Authors: Anna H. Grummon, Laura A. Gibson, Aviva A. Musicus, Alisa J. Stephens-Shields, Sophia V. Hua, Christina A. Roberto
Journal: JAMA Network Open (2023)

Policymakers and researchers have proposed a variety of interpretative front-of-package food labeling systems, but it remains unclear which is most effective at encouraging people to choose healthier foods and beverages, including among people with less education.To test the effects of 4 interpretative front-of-package food labeling systems on the healthfulness of beverage and snack selections, overall and by education level.This randomized clinical trial of a national sample of US adults 18 years and older was conducted online from November 16 to December 3, 2022.Participants were randomized to view products with 1 of 5 food labeling systems, including control (calorie labels only) or 1 of 4 interpretative labeling systems: green ("choose often") labels added to healthy foods; single traffic light labels added to healthy, moderately healthy, and unhealthy foods; physical activity calorie equivalent labels added to all products; and nutrient warning labels added to products high in calories, sugar, saturated fat, or sodium. All conditions had calorie labels on all products.Participants selected 1 of 16 beverages and 1 of 16 snacks that they wanted to hypothetically purchase. The primary outcomes were calories selected from beverages and from snacks. Secondary outcomes included label reactions and perceptions.A total of 7945 participants completed the experiment and were included in analyses (4078 [51%] female, 3779 [48%] male, and 88 [1%] nonbinary or another gender; mean [SD] age, 47.5 [17.9 years]). Compared with the control arm, exposure to the green (average differential effect [ADE], -34.2; 95% CI, -42.2 to -26.1), traffic light (ADE, -31.5; 95% CI, -39.5 to -23.4), physical activity (ADE, -39.0; 95% CI, -47.0 to -31.1), or nutrient warning labels (ADE, -28.2; 95% CI, -36.2 to -20.2) led participants to select fewer calories from beverages (all P < .001). Similarly, compared with the control label, exposure to the green (ADE, -12.7; 95% CI, -17.3 to -8.2), traffic light (ADE, -13.7; 95% CI, -18.2 to -9.1), physical activity (ADE, -18.5; 95% CI, -23.1 to -13.9), or nutrient warning labels (ADE, -14.2; 95% CI, -18.8 to -9.6) led participants to select fewer calories from snacks (all P < .001). These effects did not differ by education level. The green labels were rated as less stigmatizing than the other interpretative systems but otherwise generally received the least favorable label reactions and perceptions (eg, elicited less attention, were perceived as less trustworthy), while the nutrient warnings and physical activity labels received the most favorable ratings.In this randomized clinical trial of front-of-package food labeling systems, all 4 interpretative labeling systems reduced calories selected from beverages and from snacks compared with calorie labels, with no differences by education level.ClinicalTrials.gov Identifier: NCT05432271.
Elucidation of Pain Mechanisms in Hidradenitis Suppurativa
Authors: Sarah K. Whitley
Journal: JAMA Dermatology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Silver-integrated EDM processing of TiAl6V4 implant material has antibacterial capacity while optimizing osseointegration
Authors: Hilmar Büssemaker, Ann-Kathrin Meinshausen, Viet Duc Bui, Joachim Döring, Vadym Voropai, Adrian Buchholz, Andreas J. Mueller, Karsten Harnisch, André Martin, Thomas Berger, Andreas Schubert, Jessica Bertrand
Journal: Bioactive Materials (2023)

Periprosthetic joint infections (PJI) are a common reason for orthopedic revision surgeries. It has been shown that the silver surface modification of a titanium alloy (Ti–6Al–4V) by PMEDM (powder mixed electrical discharge machining) exhibits an antibacterial effect on Staphylococcus spp. adhesion. Whether the thickness of the silver-modified surface influences the adhesion and proliferation of bacteria as well as the ossification processes and in-vivo antibacterial capacity has not been investigated before. Therefore, the aim of this work is to investigate the antibacterial effect as well as the in vitro ossification process depending on the thickness of PMEDM silver modified surfaces. The attachment of S. aureus on the PMEDM modified surfaces was significantly lower than on comparative control samples, independently of the tested surface properties. Bacterial proliferation, however, was not affected by the silver content in the surface layer. We observed a long-term effect of antibacterial capacity in vitro, as well as in vivo. An induction of ROS, as indicator for oxidative stress, was observed in the bacteria, but not in osteoblast-like cells. No influence on the in vitro osteoblast function was observed, whereas osteoclast formation was drastically reduced on the silver surface. No changes in cell death, the metabolic activity and oxidative stress was measured in osteoblasts. We show that already small amounts of silver exhibit a significant antibacterial capacity while not influencing the osteoblast function. Therefore, PMEDM using silver nano-powder admixed to the dielectric represents a promising technology to shape and concurrently modify implant surfaces to reduce infections while at the same time optimizing bone ingrowth of endoprosthesis.
Non-erosive gastro-oesophageal reflux disease and incidence of oesophageal adenocarcinoma in three Nordic countries: population based cohort study
Authors: Dag Holmberg, Giola Santoni, My von Euler-Chelpin, Martti Färkkilä, Joonas H Kauppila, John Maret-Ouda, Eivind Ness-Jensen, Jesper Lagergren
Journal: BMJ (2023)

Abstract Objective To assess the incidence rate of oesophageal adenocarcinoma among patients with non-erosive gastro-oesophageal reflux disease compared with the general population. Design Population based cohort study. Setting All patients in hospital and specialised outpatient healthcare in Denmark, Finland, and Sweden from 1 January 1987 to 31 December 2019. Participants 486 556 adults (&gt;18 years) who underwent endoscopy were eligible for inclusion: 285 811 patients were included in the non-erosive gastro-oesophageal reflux disease cohort and 200 745 patients in the validation cohort with erosive gastro-oesophageal reflux disease. Exposures Non-erosive gastro-oesophageal reflux disease was defined by an absence of oesophagitis and any other oesophageal diagnosis at endoscopy. Erosive gastro-oesophageal reflux disease was examined for comparison reasons and was defined by the presence of oesophagitis at endoscopy. Main outcome measures The incidence rate of oesophageal adenocarcinoma was assessed for up to 31 years of follow-up. Standardised incidence ratios with 95% confidence intervals were calculated by dividing the observed number of oesophageal adenocarcinomas in each of the gastro-oesophageal reflux disease cohorts by the expected number, derived from the general populations in Denmark, Finland, and Sweden of the corresponding age, sex, and calendar period. Results Among 285 811 patients with non-erosive gastro-oesophageal reflux disease, 228 developed oesophageal adenocarcinomas during 2 081 051 person-years of follow-up. The incidence rate of oesophageal adenocarcinoma in patients with non-erosive gastro-oesophageal reflux disease was 11.0/100 000 person-years. The incidence was similar to that of the general population (standardised incidence ratio 1.04 (95% confidence interval 0.91 to 1.18)), and did not increase with longer follow-up (1.07 (0.65 to 1.65) for 15-31 years of follow-up). For validity reasons, we also analysed people with erosive oesophagitis at endoscopy (200 745 patients, 1 750 249 person-years, and 542 oesophageal adenocarcinomas, corresponding to an incidence rate of 31.0/100 000 person-years) showing an increased overall standardised incidence ratio of oesophageal adenocarcinoma (2.36 (2.17 to 2.57)), which became more pronounced with longer follow-up. Conclusions Patients with non-erosive gastro-oesophageal reflux disease seem to have a similar incidence of oesophageal adenocarcinoma as the general population. This finding suggests that endoscopically confirmed non-erosive gastro-oesophageal reflux disease does not require additional endoscopic monitoring for oesophageal adenocarcinoma.
An active HIV reservoir during ART is associated with maintenance of HIV-specific CD8+ T cell magnitude and short-lived differentiation status
Authors: Hiroshi Takata, Julie L. Mitchell, Julian Pacheco, Amélie Pagliuzza, Suteeraporn Pinyakorn, Supranee Buranapraditkun, Carlo Sacdalan, Louise Leyre, Sam Nathanson, Juyeon C. Kakazu, Jintana Intasan, Peeriya Prueksakaew, Nitiya Chomchey, Nittaya Phanuphak, Mark de Souza, Elias K. Haddad, Morgane Rolland, Sodsai Tovanabutra, Sandhya Vasan, Denise C. Hsu, Nicolas Chomont, Lydie Trautmann
Journal: Cell Host & Microbe (2023)

Before initiation of antiretroviral therapy (ART), HIV-specific CD8+ T cells are dysfunctional and short lived. To better understand the relationship between the HIV reservoir in CD4+ T cells and the magnitude and differentiation status of HIV-specific CD8+ T cells, we investigated these cells from acute and chronic HIV-infected individuals after 2 years of ART. Although both the HIV reservoir and the CD8+ T cell responses declined significantly after 2 years of ART, sustained HIV-specific CD8+ T cell responses correlated with a greater reduction of integrated HIV provirus. However, the magnitude of CD8+ T cells specific for HIV Gag, Pol, Nef, and Vif proteins positively associated with the active reservoir size during ART, measured as cell-associated RNA. Importantly, high HIV DNA levels strongly associate with maintenance of short-lived HIV-specific CD8+ T cells, regardless of ART initiation time. Our data suggest that the active reservoir maintains HIV-specific CD8+ T cell magnitude but prevents their differentiation into functional cells.
Identification of genes required for Plasmodium gametocyte-to-sporozoite development in the mosquito vector
Authors: Chiamaka Valerie Ukegbu, Ana Rita Gomes, Maria Giorgalli, Melina Campos, Alexander J. Bailey, Tanguy Rene Balthazar Besson, Oliver Billker, Dina Vlachou, George K. Christophides
Journal: Cell Host & Microbe (2023)

Malaria remains one of the most devastating infectious diseases. Reverse genetic screens offer a powerful approach to identify genes and molecular processes governing malaria parasite biology. However, the complex regulation of gene expression and genotype-phenotype associations in the mosquito vector, along with sexual reproduction, have hindered the development of screens in this critical part of the parasite life cycle. To address this, we developed a genetic approach in the rodent parasite Plasmodium berghei that, in combination with barcode sequencing, circumvents the fertilization roadblock and enables screening for gametocyte-expressed genes required for parasite infection of the mosquito Anopheles coluzzii. Our results confirm previous findings, validating our approach for scaling up, and identify genes necessary for mosquito midgut infection, oocyst development, and salivary gland infection. These findings can aid efforts to study malaria transmission biology and to develop interventions for controlling disease transmission.
Spontaneous HIV expression during suppressive ART is associated with the magnitude and function of HIV-specific CD4+ and CD8+ T cells
Authors: Mathieu Dubé, Olivier Tastet, Caroline Dufour, Gérémy Sannier, Nathalie Brassard, Gloria-Gabrielle Delgado, Amélie Pagliuzza, Corentin Richard, Manon Nayrac, Jean-Pierre Routy, Alexandre Prat, Jacob D. Estes, Rémi Fromentin, Nicolas Chomont, Daniel E. Kaufmann
Journal: Cell Host & Microbe (2023)

Spontaneous transcription and translation of HIV can persist during suppressive antiretroviral therapy (ART). The quantity, phenotype, and biological relevance of this spontaneously "active" reservoir remain unclear. Using multiplexed single-cell RNAflow-fluorescence in situ hybridization (FISH), we detect active HIV transcription in 14/18 people with HIV on suppressive ART, with a median of 28/million CD4+ T cells. While these cells predominantly exhibit abortive transcription, p24-expressing cells are evident in 39% of participants. Phenotypically diverse, active reservoirs are enriched in central memory T cells and CCR6- and activation-marker-expressing cells. The magnitude of the active reservoir positively correlates with total HIV-specific CD4+ and CD8+ T cell responses and with multiple HIV-specific T cell clusters identified by unsupervised analysis. These associations are particularly strong with p24-expressing active reservoir cells. Single-cell vDNA sequencing shows that active reservoirs are largely dominated by defective proviruses. Our data suggest that these reservoirs maintain HIV-specific CD4+ and CD8+ T responses during suppressive ART.
Better together: Non-additive interactions between schizophrenia risk genes
Authors: P.J. Michael Deans, Kristen J. Brennand
Journal: Cell Genomics (2023)

Zhang, Zhang, Forrest et al combine allele-specific open chromatin (ASoC) mapping and CRISPR-editing to evaluate the functional impact of schizophrenia risk variants on human neuronal gene expression, synaptic development, and function. In doing so, they uncover surprising non-additive effects between target genes regulated by the same risk variant.